School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
Adv Clin Chem. 2013;60:1-63. doi: 10.1016/b978-0-12-407681-5.00001-5.
Mechanisms postulated to link folate and B12 metabolism with cancer, including genome-wide hypomethylation, gene-specific promoter hypermethylation, and DNA uracil misincorporation, have been observed in prostate tumor cells. However, epidemiological studies of prostate cancer risk, based on dietary intakes and blood levels of folate and vitamin B12 and on folate-pathway gene variants, have generated contradictory findings. In a meta-analysis, circulating concentrations of B12 (seven studies, OR = 1.10; 95% CI 1.01, 1.19; P = 0.002) and (in cohort studies) folate (five studies, OR = 1.18; 95% CI 1.00, 1.40; P = 0.02) were positively associated with an increased risk of prostate cancer. Homocysteine was not associated with risk of prostate cancer (four studies, OR = 0.91; 95% CI 0.69, 1.19; P = 0.5). In a meta-analysis of folate-pathway polymorphisms, MTR 2756A > G (eight studies, OR = 1.06; 95% CI 1.00, 1.12; P = 0.06) and SHMT1 1420C > T (two studies, OR = 1.11; 95% CI 1.00, 1.22; P = 0.05) were positively associated with prostate cancer risk. There were no effects due to any other polymorphisms, including MTHFR 677C > T (12 studies, OR = 1.04; 95% CI 0.97, 1.12; P = 0.3). The positive association of circulating B12 with an increased risk of prostate cancer could be explained by reverse causality. However, given current controversies over mandatory B12 fortification, further research to eliminate a causal role of B12 in prostate cancer initiation and/or progression is required. Meta-analysis does not entirely rule out a positive association of circulating folate with increased prostate cancer risk. As with B12, even a weak positive association would be a significant public health issue, given the high prevalence of prostate cancer and concerns about the potential harms versus benefits of mandatory folic acid fortification.
已在前列腺肿瘤细胞中观察到叶酸和 B12 代谢与癌症相关的机制，包括全基因组低甲基化、基因特异性启动子超甲基化和 DNA 尿嘧啶掺入错误。然而，基于饮食摄入、血液中叶酸和维生素 B12 水平以及叶酸途径基因变异的前列腺癌风险的流行病学研究得出了相互矛盾的结果。在荟萃分析中，B12（7 项研究，OR = 1.10；95%CI 1.01，1.19；P = 0.002）和叶酸（5 项研究，OR = 1.18；95%CI 1.00，1.40；P = 0.02）的循环浓度与前列腺癌风险增加呈正相关。同型半胱氨酸与前列腺癌风险无关（4 项研究，OR = 0.91；95%CI 0.69，1.19；P = 0.5）。在叶酸途径多态性的荟萃分析中，MTR 2756A > G（8 项研究，OR = 1.06；95%CI 1.00，1.12；P = 0.06）和 SHMT1 1420C > T（2 项研究，OR = 1.11；95%CI 1.00，1.22；P = 0.05）与前列腺癌风险呈正相关。其他多态性无影响，包括 MTHFR 677C > T（12 项研究，OR = 1.04；95%CI 0.97，1.12；P = 0.3）。B12 循环与前列腺癌风险增加之间的正相关可能是由于反向因果关系。然而，鉴于目前对强制 B12 强化的争议，需要进一步的研究来消除 B12 在前列腺癌起始和/或进展中的因果作用。荟萃分析并不能完全排除循环叶酸与前列腺癌风险增加之间的正相关。与 B12 一样，即使是微弱的正相关也将是一个重大的公共卫生问题，因为前列腺癌的高患病率以及对强制叶酸强化的潜在危害与益处的担忧。
